At least 20 clinically relevant factors affect percutaneous absorption of drugs and chemicals: relevant physicochemical properties, vehicle/formulation, drug exposure conditions (dose, duration, surface area, and exposure frequency), skin appendages (hair follicles and glands) as sub-anatomical pathways, skin application sites (regional variation in penetration), population variability (premature, infants, and aged), skin surface conditions (hydration, temperature, and pH), skin health and integrity (trauma and skin diseases), substantivity and binding to different skin components, systemic distribution and systemic toxicity, stratum corneum exfoliation, washing-off and washing-in, rubbing/massaging, transfer to others (human to human and hard surface to human), volatility, metabolic biotransformation/cutaneous metabolism, photochemical transformation and photosensitivity, excretion kinetics, lateral spread, and chemical method of determining percutaneous absorption.